RARE DISEASE
Lead poisoning
Lead poisoning
Lead poisoning
Synonyms: Lead intoxication, Plumbism, Saturnism
Synonyms: Lead intoxication, Plumbism, Saturnism
Synonyms: Lead intoxication, Plumbism, Saturnism
Drug discovery
3
drugs
With orphan designations
Overview
Lead poisoning is a systemic toxicosis caused by lead accumulation, primarily affecting neurological development in children and cardiovascular/renal function in adults. Exposure occurs through lead-based paint, contaminated soil/water, and occupational sources. Diagnosis relies on venous blood lead levels (BLL), with treatment focused on exposure cessation and chelation therapy for BLL ≥45 μg/dL. Neurocognitive effects are often irreversible, emphasizing prevention [1][6][15][16].
Population
Children <6 years account for 80% of global cases due to hand-to-mouth behavior and higher absorption rates [2][9]
High-risk groups: Residents of pre-1978 housing, battery/recycling workers, and communities with poor lead regulation [7][12][17]
800 million+ children globally have BLL ≥5 μg/dL; 30x higher prevalence in low-income countries [9][14]
Burden
Therapies
Primary intervention: Source identification/removal + nutritional optimization (iron/calcium) [6][8][11]
Chelation 1) Oral DMSA for BLL 45-69 μg/dL 2) IV CaNa₂EDTA for BLL ≥70 μg/dL or encephalopathy [3][13][16]
Monitoring: Weekly BLL checks during chelation + environmental hazard mitigation [6][11]
Categories: rare disorders due to toxic effects
Research Papers
1,475 drug discovery papers about Lead poisoning, with 1 first-in-class and 4 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
1,475 drug discovery papers about Lead poisoning, with 1 first-in-class and 4 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
categories:
Small molecules
proteins
2022-05-31 | Oyster (Crassostrea gigas) ferritin can efficiently reduce the damage of Pb2+in vivo by electrostatic attraction.
Heavy metal ions pollution can cause damage to human body through food, so the development of a new kind of macromolecular that can remove heavy metal ions damage has a good application prospect. The possibilities of removing heavy metal ions from food system with ferritin were studied in this paper. In this study, oyster ferritin (GF1) can resistant to denaturation induced by Pb2+, Cd2+, Cr3+ and still maintains its basic structure. GF1 can bind more Pb2+, Cd2+, Cr3+ than recombinant human H-chain ferritin (rHuHF), especially Pb2+, and the findings suggest that each GF1 can capture about 51.42 Pb2+ in solution. The hard and soft acids and base also verifies that Pb2+ have stronger binding ability to the key amino acids at the outer end of the three-fold symmetry channel. Cells preprotected by ferritin could resistant to heavy metal ions. And GF1 can reduce the high blood lead in mice and may play a role in alleviating lead poisoning in vivo. All findings demonstrated that GF1 can be used as a novel macromolecule to bind heavy metal ions, and the study can broaden the research scope of ferritin in contaminated food systems.
2021-12-21 | Versatile Cell and Animal Models for Advanced Investigation of Lead Poisoning.
The heavy metal, lead (Pb) can irreversibly damage the human nervous system. To help understand Pb-induced damage, we applied a genetically encoded Förster resonance energy transfer (FRET)-based Pb biosensor Met-lead 1.44 M1 to two living systems to monitor the concentration of Pb: induced pluripotent stem cell (iPSC)-derived cardiomyocytes as a semi-tissue platform and Drosophila melanogaster fruit flies as an in vivo animal model. Different FRET imaging modalities were used to obtain FRET signals, which represented the presence of Pb in the tested samples in different spatial dimensions. Using iPSC-derived cardiomyocytes, the relationship between beating activity (20-24 beats per minute, bpm) determined from the fluctuation of fluorescent signals and the concentrations of Pb represented by the FRET emission ratio values of Met-lead 1.44 M1 was revealed from simultaneous measurements. Pb (50 μM) affected the beating activity of cardiomyocytes, whereas two drugs that stop the entry of Pb differentially affected this beating activity: verapamil (2 μM) did not reverse the cessation of beating, whereas 2-APB (50 μM) partially restored this activity (16 bpm). The results clearly demonstrate the potential of this biosensor system as an anti-Pb drug screening application. In the Drosophila model, Pb was detected within the adult brain or larval central nervous system (Cha-gal4 > UAS-Met-lead 1.44 M1) using fast epifluorescence and high-resolution two-photon 3D FRET ratio image systems. The tissue-specific expression of Pb biosensors provides an excellent opportunity to explore the possible Pb-specific populations within living organisms. We believe that this integrated Pb biosensor system can be applied to the prevention of Pb poisoning and advanced research on Pb neurotoxicology.
2021-07-30 | Harnessing Peptides against lead pollution and poisoning: Achievements and prospects.
Among the broad applicability of peptides in numerous aspects of life and technologies, their interactions with lead (Pb), one of the most harmful substances to the environment and health, are constantly explored. So far, peptides were developed for environmental remediation of Pb-contaminations by various strategies such as hydrogelation and surface display. They were also designed for Pb detection and sensing by electrochemical and fluorescent methods and for modeling natural proteins that involve in mechanisms by which Pb is toxic. This review aims at summarizing selected examples of these applications, manifesting the enormous potential of peptides in the combat against Pb pollution. Nevertheless, the absence of new medicinal treatments against Pb poisoning that are based on peptides is noticeable. An overview of previous achievements utilizing Pb-peptide interactions towards various goals is presented and can be therefore leveraged to construct a useful toolbox for the design of smart peptides as next-generation therapeutics against Pb.
2019-11-04 | Therapeutic implications of how TNF links apolipoprotein E, phosphorylated tau, α-synuclein, amyloid-β and insulin resistance in neurodegenerative diseases.
While cytokines such as TNF have long been recognized as essential to normal cerebral physiology, the implications of their chronic excessive production within the brain are now also increasingly appreciated. Syndromes as diverse as malaria and lead poisoning, as well as non-infectious neurodegenerative diseases, illustrate this. These cytokines also orchestrate changes in tau, α-synuclein, amyloid-β levels and degree of insulin resistance in most neurodegenerative states. New data on the effects of salbutamol, an indirect anti-TNF agent, on α-synuclein and Parkinson's disease, APOE4 and tau add considerably to the rationale of the anti-TNF approach to understanding, and treating, these diseases. Therapeutic advances being tested, and arguably useful for a number of the neurodegenerative diseases, include a reduction of excess cerebral TNF, whether directly, with a specific anti-TNF biological agent such as etanercept via Batson's plexus, or indirectly via surgically implanting stem cells. Inhaled salbutamol also warrants investigating further across the neurodegenerative disease spectrum. It is now timely to integrate this range of new information across the neurodegenerative disease spectrum, rather than keep seeing it through the lens of individual disease states.
2016-05-24 | Lead Poisoning Disturbs Oligodendrocytes Differentiation Involved in Decreased Expression of NCX3 Inducing Intracellular Calcium Overload.
Lead (Pb) poisoning has always been a serious health concern, as it permanently damages the central nervous system. Chronic Pb accumulation in the human body disturbs oligodendrocytes (OLs) differentiation, resulting in dysmyelination, but the molecular mechanism remains unknown. In this study, Pb at 1 μM inhibits OLs precursor cells (OPCs) differentiation via decreasing the expression of Olig 2, CNPase proteins in vitro. Moreover, Pb treatment inhibits the sodium/calcium exchanger 3 (NCX3) mRNA expression, one of the major means of calcium (Ca(2+)) extrusion at the plasma membrane during OPCs differentiation. Also addition of KB-R7943, NCX3 inhibitor, to simulate Pb toxicity, resulted in decreased myelin basic protein (MBP) expression and cell branching. Ca(2+) response trace with Pb and KB-R7943 treatment did not drop down in the same recovery time as the control, which elevated intracellular Ca(2+) concentration reducing MBP expression. In contrast, over-expression of NCX3 in Pb exposed OPCs displayed significant increase MBP fluorescence signal in positive regions and CNPase expression, which recovered OPCs differentiation to counterbalance Pb toxicity. In conclusion, Pb exposure disturbs OLs differentiation via affecting the function of NCX3 by inducing intracellular calcium overload.
small molecules
2026-09-17 | Lead exposure decreases TPMT activity, highlighting the need for thiopurine dose adjustment in high-exposure individuals.
Thiopurine drugs are used for the treatment of a wide variety of diseases ranging from autoimmune diseases to various leukemia types. As efficacy of thiopurine drugs is significantly reduced by Thiopurine S-methyltransferase (TPMT)-mediated S-methylation, accurate assessment of individual TPMT-activity levels is crucial for optimizing thiopurine drug dosage regimens for each patient. Given its multifaceted regulation, identifying occupational exposures impacting TPMT enzymatic activity is crucial. The influence of lead(Pb2 +) on the enzymatic activity of TPMT was initially assessed in vitro, by spiking human blood having normal TPMT levels with increasing levels of Pb2+. The effect of occupational Pb2+-exposure on TPMT activity was further investigated by comparing blood TPMT activity levels of industrial workers prone to occupational Pb2+-exposure. Putative Pb2+-docking sites on TPMT enzyme were assessed through in silico analysis via MIB2 and CB-Dock2 servers. In vitro analysis indicated an inverse correlation between blood Pb2+-levels and TPMT-activity, which was further supported by in vivo analyses, providing evidence for Pb2+-mediated TPMT-inactivation. In silico Pb2+-docking analyses suggest two putative regions for Pb2+-mediated competitive TPMT-inhibition, four regions for direct/indirect inhibition, and four regions for allosteric inhibition. Further kinetic studies suggest that Pb2+ exerts its inhibitory effect through competition with SAM for the active site. The observed inverse correlation between blood Pb2+ and TPMT levels emphasizes the clinical importance of individualizing thiopurine drug dosage, especially for patients exposed to high levels of Pb2+. In vitro studies involving site-directed mutagenesis and analysis of patients with Pb2+-binding site mutations will validate the precise Pb2+-binding sites involved in TPMT-inhibition.
2026-09-08 | Therapeutics are needed to ameliorate neurobehavioral symptoms of developmental lead poisoning.
Developmental lead poisoning is a global problem and requires a global effort to remedy the environment and its effect on children. Until environmental lead is eliminated, therapeutics should be developed to alleviate symptoms of developmental lead poisoning. Memory and learning require adaptive oligodendrogenesis and neomyelination. Lead poisoning causes memory and learning deficits by targeting oligodendroglia lineage cells as well as other cells of the central nervous system. Though the etiologies of the various diseases and conditions that exhibit memory deficits being considered for treatment with pro-oligodendrogenesis therapeutics are different, the affected individuals share with those who have developmental lead intoxication the common symptoms of memory and cognitive deficits. Yet, unlike these maladies, there have not been any reports of studies exploring the use of pro-oligodendrogenesis drugs to ameliorate the memory/learning deficits in pediatric lead poisoning. The public health and science communities should recognize the consequence of developmental lead poisoning on society and deliver relief to the affected children with a low cost oral drug while maintaining the long term goal of ridding the planet of environmental lead contamination.
2026-09-04 | MORPHOLOGICAL CHARACTERISTICS OF REPARATIVE OSTEOGENESIS UNDER CONDITIONS OF CHRONIC LEAD INTOXICATION DURING PHARMACOLOGICAL CORRECTION IN AN EXPERIMENT
Aim — to assess the effect of combined metabolic correction (succinic acid, calcium citrate, vitamin D₃) on the morphological dynamics of reparative osteogenesis under ongoing lead intoxication. Materials and methods. Fifteen rats of experimental group II received water with lead acetate (50 mg/kg); after creation of a monocortical defect of the right femoral diaphysis (week 4, diameter 1.0 mm) the diet was supplemented with succinic acid (100 mg/kg), calcium citrate (200 mg/kg) and vitamin D₃ (500 IU/kg). Animals were withdrawn on days 7, 14, 21 and 28; sections were stained with haematoxylin–eosin and Masson trichrome (×100, ×400). Results. Under correction, repair proceeded more actively than in untreated animals: as early as day 7 angiogenesis and osteoblastic activity recovered, inflammatory infiltration and haemorrhages were absent, and cartilage fragments appeared. By days 14–21 a well-consolidated callus formed with compact, better-mineralised trabeculae and signs of woven-to-lamellar remodelling. By day 28 the callus consisted predominantly of mature lamellar bone with restored architecture, although isolated dystrophic osteocytes persisted. Conclusion. Combined metabolic correction substantially improves reparative osteogenesis under lead intoxication, bringing the morphological picture closer to physiological, yet not reaching the level of intact animals.
2026-09-04 | The Chemical Domino Effect: Lead Poisoning and the Collapse of Late Bronze Age Elites
Late Bronze Age collapse, Lead poisoning, Archaeometallurgy, Palace economies, Tin shortage
2026-09-03 | Ameliorative Role of fenugreek Oil Against Lead Acetate Trihydrate-Induced Hepatic, Renal and Testicular Injury in Wistar Albino Rats: Insights into Bcl-2 Expression and sodium/potassium balance.
Lead (Pb) is a prevalent environmental toxicant that induces multisystem toxicity, primarily through oxidative stress and apoptosis. Trigonella foenum-graecum L. (fenugreek) seed oil is enriched with bioactive phytoconstituents possessing potent antioxidant and anti-inflammatory properties. Therefore, this study was designed to investigate the protective effect of fenugreek oil against lead acetate trihydrate (PbAc)-induced hepatic, renal, and testicular histopathological damage in Wistar rats, with emphasis on the anti-apoptotic marker (Bcl-2). A total of 40 rats were randomly divided into four experimental groups (10 in each): a control group (CG), a Pb-intoxicated group (PbG) given 50 mg/kg of PbAc daily, a fenugreek oil-protected group (Pb + FOG) co-administered the same PbAc dose plus 250 mg/kg of fenugreek, and fenugreek oil-only group (FOG) receiving 250 mg/kg of fenugreek oil alone. All treatments were administered via oral gavage over a period of four weeks. Histopathological examination of the PbG revealed marked structural alterations in the hepatic tissue (necrosis, cytoplasmic vacuolation, and inflammatory cell infiltration), renal tissue (glomerular shrinkage and tubular degeneration), and testicular tissue (degeneration of the germinal epithelium and Leydig cells) compared to the CG. In contrast, co-administration of fenugreek seed oil in the Pb + FOG partially restored histological architecture of hepatic, renal and testicular tissues compared to the PbG. However, co-administration of fenugreek seed oil in the Pb + FOG significantly upregulated Bcl-2 mRNA expression compared to PbG (0.65 vs. 0.40; P < 0.01). Sequencing analysis of liver samples showed 97.81-100% nucleotide identity with the Bcl-2 mRNA reference sequence. Lead intoxication in the PbG significantly impaired serum biochemical parameters and elevated Na⁺, K⁺, and Pb levels compared to the CG and FOG. Conversely, co-administration of fenugreek seed oil in the Pb + FOG significantly reduced Pb concentration and restored Na⁺/K⁺ levels. In conclusion, concurrent administration of fenugreek seed oil may attenuate PbAc-induced hepatic, renal and testicular histopathological damage in rats. This protectivity effect was associated with the restoration of sodium/potassium balance, and upregulation of Bcl-2 expression. Nonetheless, further mechanistic studies, particularly addressing oxidative stress markers, are required.
oligonucleotides
2025-10-18 | Dual-Action Cellular Nanoparticles for Effective Lead (Pb2+) Detoxification.
Lead (Pb2+) exposure remains a persistent and serious public health concern due to its widespread presence and profound toxicity. Building on recent advances in toxin-neutralizing cell membrane-coated nanoparticles (CNPs) and the discovery of Pb2+-binding DNA aptamers, we develop dual-action neuron-mimetic CNPs for effective Pb2+ detoxification. In the formulation, the CNPs encapsulate aptamers within metal-organic framework (MOF) cores and coated with membranes derived from SH-SY5Y neuroblastoma cells, two functional components working together to neutralize Pb2+. The resulting constructs, termed Neuron-MOF/aptamer-NPs, exhibit strong Pb2+ binding capacity, excellent colloidal stability in physiological media, and resistance to DNA leakage. In vitro assays identify Neuron-MOF/aptamer-NPs as the most potent formulation, demonstrating dual-action neutralization against Pb2+-induced toxicity, oxidative stress, and lipid peroxidation in SH-SY5Y cells. In vivo, Neuron-MOF/aptamer-NP treatment significantly improves survival in a mouse model of lead poisoning and reduces hematologic, hepatic, and renal damage. Behavioral assessments further confirm the restoration of spatial memory and locomotor function. Neuron-MOF/aptamer-NPs exhibit no signs of acute toxicity in healthy mice. These findings establish Neuron-MOF/aptamer-NPs as a potent and biocompatible therapeutic platform for targeted lead detoxification with systemic and neuroprotective benefits.
2022-05-02 | Targeting CC chemokine ligand (CCL) 20 by miR-143-5p alleviate lead poisoning-induced renal fibrosis by regulating interstitial fibroblasts excessive proliferation and dysfunction.
Environmental lead contamination can cause chronic renal disease with a common clinical manifestation of renal fibrosis and constitutes a major global public health threat. Aberrant proliferation and extracellular matrix (ECM) accumulation in renal interstitial fibroblasts are key pathological causes of renal fibrosis. However, the mechanism underlying lead-induced kidney fibrosis remains unclear. The present study analyzed gene expression prolifes in lead acetate-treated primary mice renal interstitial fibroblasts and confirmed the aberrant expression of CC chemokine ligand (CCL) 20, one of the most obvious up-regulated genes. Analogously, lead acetate exposure dose-dependently increased CCL20 transcription, protein expression and release. Knockdown of CCL20 suppressed lead acetate-induced fibroblast proliferation, hydroxyproline contents, transforming growth factor-beta production and ECM-related protein (Collagen I and fibronectin) expression. Bioinformatics analysis predicted five top miRNAs targeting CCL20. Among them, miR-143-5p expression was dose-dependently decreased in lead acetate-treated fibroblasts. Mechanistically, miR-143-5p directly targeted CCL20. Elevation of miR-143-5p antagonized lead acetate-induced fibroblast proliferation, hydroxyproline and ECM-related protein expression, which were reversed by CCL20 overexpression. Additionally, CCL20 knockdown suppressed lead acetate-mediated Smad2/3 and AKT pathway activation. Notably, miR-143-5p overexpression attenuated the activation of the Smad2/3 and AKT pathway in lead acetate-exposed fibroblasts, which was counteracted by CCL20 elevation. miR-143-5p injection ameliorated renal fibrosis progression in mice in vivo. Thus, targeting CCL20 by miR-143-5p could alleviate renal fibrosis progression by regulating fibroblast proliferation and ECM deposition via the Smad2/3 and AKT signaling, providing a potential therapeutic target for environmental lead contamination-evoked fibrotic kidney disease.
2021-04-28 | Pb exposure triggers MAPK-dependent inflammation by activating oxidative stress and miRNA-155 expression in carp head kidney.
Lead (Pb) is a toxic heavy metal and an aquatic pollutant. Various amounts of heavy metals are released into the environment through industrial discharge, causing excessive contamination of aquatic ecosystems. The head kidney is a unique immune organ of the bony fish and plays an important role in the metabolism of heavy metals. Studies of toxic Pb exposure that have investigated the head kidney of carp are limited. This study was carried out to explore the potential immunotoxicity effects of Pb and the specific related mechanisms in the carp head kidney. Pb poisoning was shown to induce the production of reactive oxygen species (ROS) and increase the expression levels of phosphorylated proteins related to the MAPK pathway, including p38, extracellular signal-regulated protein kinase (ERK), and c-Jun N-terminal kinase (JNK). We also found that microRNA-155 played a key role in regulating the production of inflammatory factors TNF-α, IL-1β, and IL-6, and the pre-miRNA-155 inhibitor reversed the Pb-induced inflammation. In conclusion, these in vitro and in vivo findings suggest that oxidative stress and the MAPKs are involved in the Pb-induced inflammasome response, and the production of microRNA-155 aggravated the occurrence of inflammation in carp head kidney.
2019-03-18 | Chronic lead exposure decreases the expression of Huntingtin-associated protein 1 (HAP1) through Repressor element-1 silencing transcription (REST).
Chronic lead (Pb) exposure has been shown to reduce the expression of some synaptic proteins which are involved in vesicular trafficking and affect presynaptic neurotransmitter release. However, the precise mechanisms by Pb impairs neurotransmitter release are still not well defined. In the current study, we aimed to elucidate the changes of Huntingtin-associated protein 1 (HAP1) in Pb exposed rats and PC12 cells models and its molecular mechanism. Repressor element-1 silencing transcription (REST) modulates the expression of genes containing the repressor element 1 (RE-1) cis-regulatory DNA sequence. HAP1 promoter region contains a RE-1 binding motif. We also observed whether Pb exposure regulated the HAP1 transcription level through influencing the expression of REST. Mother rats were exposed to 0.5 and 2 g/L Pb acetate (PbAc) in drinking water from the first day of gestation until postnatal 21 days, then the offspring rats were continued to drink PbAc for 1 year, while the control groups received drinking water. PC12 cells were divided into 3 groups: 0 μM, 1 μM and 100 μM PbAc. The results revealed that Pb levels in blood and brain of Pb exposed groups were significantly higher than that of the control group. The ability of learning and memory in Pb exposed rats was decreased. Pb exposure reduced the expression of HAP1 and increased the REST expression. Silencing REST could reverse the decreasing of HAP1 in Pb exposed PC12 cells. Our findings raise a possibility that the decreasing of HAP1 expression by Pb exposure may affect neurotransmitter release and results in impairments in spatial learning and memory ability.
2018-12-28 | Lead exposure inhibits expression of SV2C through NRSF.
Lead (Pb) exposure has been shown to affect presynaptic neurotransmitter release in the animal and cell models. The mechanism by which Pb exposure impairs neurotransmitter release remains unknown. In this study, we aimed to investigate the effect of Pb exposure on synaptic vesicle protein 2C (SV2C) and its molecular mechanism. SV2C promoter region contains a neuron-restrictive silencer element (NRSE) binding motif. Neuron-restrictive silencer factor (NRSF) is a transcription repressor that regulates gene expression by binding to NRSE. We also observed whether Pb exposure regulates the transcriptional level of SV2C by influencing the expression of NRSF. Pregnant female rats were exposed to 0, 0.5 and 2.0 g/L lead acetate (PbAc) via drinking water from the first day of gestation until postnatal week 3. Neuro-2a (N2a) cells were divided into 3 groups: 0 μM (control group), 1 μM and 100 μM PbAc. Our data revealed that the ability of learning and memory in Pb-exposed rats were decreased, Pb exposure decreased SV2C expression and increased NRSF expression in the rat hippocampus and N2a cell. Silencing NRSF can reverse the down-regulation of Pb exposure on SV2C. These results indicate that Pb exposure can inhibit the transcription level of SV2C by up regulating the expression of NRSF. Decreased expression of SV2C can affect neurotransmitter release and synaptic transmission, which affect synaptic plasticity and then result in impairment of learning and memory.
cell therapies
2026-09-27 | Engineered Probiotics with Pb-Binding Enhanced Curli Nanofibers for Oral Lead Elimination.
Lead poisoning remains a persistent global health challenge. Current small-molecule chelation therapies for lead poisoning cause systemic side effects due to non-specific metal depletion. Here, we propose an "affinity-selectivity-safety" strategy using a living biointerface in which the probiotic is programmed to overexpress customized curli nanofibers. The high-affinity Pb-binding protein PbrR was anchored onto the cell surface of Escherichia coli Nissle 1917 (EcN) via fusion to the curli nanofiber subunit CsgA and presented within the extracellular self-assembled curli network. After induction, EcNC-P overexpresses the C-P fusion protein, which self-assembles into a dense and stable network of PbrR-functionalized curli nanofibers on the bacterial surface, without impairing bacterial viability, intestinal transit properties, or intrinsic probiotic functions. The engineered probiotics exhibited an exceptional Pb2+ binding capacity of up to 70 mg·g-1 biomass and preferential Pb selectivity over essential metals under competitive conditions. The curli-displayed PbrR provides an array of multidentate Pb2+-chelating sites, endowing the living material with an ultrahigh lead adsorption capacity. Orally ingested EcNC-P was completely excreted within 12 h, ensuring biosafety. In an acute oral Pb exposure mouse model, EcNC-P-based living materials achieved better efficacy than orally administered DTPA under the same dosing condition, reducing blood Pb levels by ∼30% and increasing fecal Pb excretion by ∼1.2-fold. Therapeutic supplementation of the probiotics promoted fecal lead excretion and markedly decreased tissue lead burdens and was associated with alleviated intestinal inflammation and altered gut microbiota composition. No systemic toxicity or adverse effects were observed with single high-dose use. This surface-anchored customized curli nanofiber probiotic integrates high-affinity lead chelation with the bioactivities of a living biointerface, offering a safe, oral, and programmable platform for the holistic management of lead poisoning.
2024-02-09 | Screening and Identification of Probiotic Lactobacilli from the Infant Gut Microbiota to Alleviate Lead Toxicity.
Lead (Pb2+) exposure cause a potential hazard to human health and the ecological environment; however, prevention and treatment of Pb2+ toxicity remain problems. The aim of this study is to isolate a novel probiotic lead (Pb2+)-resistant Lactobacillus strain from the infant gut microbiota and to determine whether they have the probiotic properties and investigate its preventive and therapeutic effects in the early-life Pb2+ exposure mouse model. In the present study, a total of 64 Pb2+-resistant colonies were isolated from the infant gut microbiota. Of these colonies, SYF-08, identified as Lacticaseibacillus casei, exhibited a Pb2+-binding capacity and Pb2+ tolerance. The in vivo study showed that SYF-08 treatment could effectively reduce Pb2+ levels in the blood, alleviate Pb2+ enrichment in bone and brain tissues, and recover the intestinal and brain damage in both dams and offspring. SYF-08 treatment also improved the antioxidant index in the liver and kidney tissues, while increasing the diversity of the intestinal microbiota of the offspring. The results of the in vitro and in vivo studies suggest that SYF-08, isolated from infant fecal samples, is a promising candidate probiotic against Pb2+ toxicity.
2023-02-06 | Lactobacillus fermentum HNU312 alleviated oxidative damage and behavioural abnormalities during brain development in early life induced by chronic lead exposure.
Lead exposure is a global public health safety issue that severely disrupts brain development and causes damage to the nervous system in early life. Probiotics and gut microbes have been highlighted for their critical roles in mitigating lead toxicity. However, the underlying mechanisms by which they work yet to be fully explored. Here, we designed a two-stage experiment using the probiotic Lactobacillus fermentum HNU312 (Lf312) to uncover how probiotics alleviate lead toxicity to the brain during early life. First, we explored the tolerance and adsorption of Lf312 to lead in vitro. Second, the adsorption capacity of the strain was determined and confirmed in vivo. The shotgun metagenome sequencing showed lead exposure-induced imbalance and dysfunction of the gut microbiome. In contrast, Lf312 intake significantly modulated the structure of the microbiome, increased the abundance of beneficial bacteria and short-chain fatty acids (SCFAs)-producing bacteria, and upregulated function-related metabolic pathways such as antioxidants. Notably, Lf312 enhanced the integrity of the blood-brain barrier by increasing the levels of SCFAs in the gut, alleviated inflammation in the brain, and ultimately improved anxiety-like and depression-like behaviours induced by lead exposure in mice. Subsequently, the effective mechanism was confirmed, highlighting that Lf312 worked through integrated strategies, including ionic adsorption and microbiota-gut-brain axis regulation. Collectively, this work elucidated the mechanism by which the gut microbiota mitigates the toxic effects of lead in the brain and provides preventive measures and intervention measures for brain damage due to mass lead poisoning in children.
2022-08-10 | Lactobacillus plantarum WSJ-06 alleviates neurobehavioral injury induced by lead in mice through the gut microbiota.
Chronic lead exposure can result in cognitive dysfunction and behavioral disorders. However, the current treatments for alleviating lead poisoning have many side effects. Previous studies have suggested that probiotics may have the potential to ameliorate neurotoxicity caused by lead exposure. This study determines the alleviating effects of Lactobacillus plantarum WSJ-06 on neurological disorders induced by chronic lead exposure from the perspective of the gut microbiota and serum metabolites. The results showed that treatment with Lactobacillus plantarum WSJ-06 alleviated memory dysfunction and reduced the levels of inflammatory cytokines in the serum and hippocampus induced by lead exposure. In addition, Lactobacillus plantarum WSJ-06 partially restored the lead-induced gut microbiota dysbiosis. It also increased the proportion of some beneficial metabolites in the serum, such as arachidonic acid, tryptophan hydroxylase, serotonin, vitamin B12, trehalose, and kynurenic acid, and decreased some metabolites in the serum, such as LPS 20:5 and L-kynurenine. A correlation analysis further indicated that lead-induced neurobehavioral disorders were related to intestinal microbiota (the [Eubacterium]_siraeum_group, Roseburia, Lactobacillus, etc) and serum metabolites (LPS 20:5, serotonin, vitamin B12, etc). In conclusion, Lactobacillus plantarum WSJ-06 alleviated neuroinflammation and memory impairment caused by lead exposure by modulating the gut microbiota and metabolites in the serum.
2019-10-29 | Bio‐Orthogonal Bacterial Reactor for Remission of Heavy Metal Poisoning and ROS Elimination
Multitudinous industrial products in daily life put human health at risk of heavy metal exposure, and natural bacteria have displayed superior performance in bioadsorption and biodegradation of heavy metal. In this study, a bacteria-based bioreactor is developed to precisely bioadsorb lead (Pb) ions, eliminate concomitant reactive oxygen species (ROS), and remit the injury of acute/chronic Pb poisoning. A nonpathogenic bacteria Escherichia coli MG1655 (Bac) is decorated with antioxidative cerium oxide nanoparticles (Ceria) on the surface through a bio-orthogonal reaction, and the complex bioreactor could spontaneously aggregate in organs with high concentration of Pb. Furthermore, the excess Pb is bioadsorbed by bacteria and the concomitant ROS is eliminated by Ceria nanoparticles. In vitro and in vivo studies demonstrate that this integral biotic/abiotic hybrid bioreactor successfully realizes detoxication of Pb and reparation of injury, also accompanied with inappreciable side effects.
proteins
2022-05-31 | Oyster (Crassostrea gigas) ferritin can efficiently reduce the damage of Pb2+in vivo by electrostatic attraction.
Heavy metal ions pollution can cause damage to human body through food, so the development of a new kind of macromolecular that can remove heavy metal ions damage has a good application prospect. The possibilities of removing heavy metal ions from food system with ferritin were studied in this paper. In this study, oyster ferritin (GF1) can resistant to denaturation induced by Pb2+, Cd2+, Cr3+ and still maintains its basic structure. GF1 can bind more Pb2+, Cd2+, Cr3+ than recombinant human H-chain ferritin (rHuHF), especially Pb2+, and the findings suggest that each GF1 can capture about 51.42 Pb2+ in solution. The hard and soft acids and base also verifies that Pb2+ have stronger binding ability to the key amino acids at the outer end of the three-fold symmetry channel. Cells preprotected by ferritin could resistant to heavy metal ions. And GF1 can reduce the high blood lead in mice and may play a role in alleviating lead poisoning in vivo. All findings demonstrated that GF1 can be used as a novel macromolecule to bind heavy metal ions, and the study can broaden the research scope of ferritin in contaminated food systems.
2021-12-21 | Versatile Cell and Animal Models for Advanced Investigation of Lead Poisoning.
The heavy metal, lead (Pb) can irreversibly damage the human nervous system. To help understand Pb-induced damage, we applied a genetically encoded Förster resonance energy transfer (FRET)-based Pb biosensor Met-lead 1.44 M1 to two living systems to monitor the concentration of Pb: induced pluripotent stem cell (iPSC)-derived cardiomyocytes as a semi-tissue platform and Drosophila melanogaster fruit flies as an in vivo animal model. Different FRET imaging modalities were used to obtain FRET signals, which represented the presence of Pb in the tested samples in different spatial dimensions. Using iPSC-derived cardiomyocytes, the relationship between beating activity (20-24 beats per minute, bpm) determined from the fluctuation of fluorescent signals and the concentrations of Pb represented by the FRET emission ratio values of Met-lead 1.44 M1 was revealed from simultaneous measurements. Pb (50 μM) affected the beating activity of cardiomyocytes, whereas two drugs that stop the entry of Pb differentially affected this beating activity: verapamil (2 μM) did not reverse the cessation of beating, whereas 2-APB (50 μM) partially restored this activity (16 bpm). The results clearly demonstrate the potential of this biosensor system as an anti-Pb drug screening application. In the Drosophila model, Pb was detected within the adult brain or larval central nervous system (Cha-gal4 > UAS-Met-lead 1.44 M1) using fast epifluorescence and high-resolution two-photon 3D FRET ratio image systems. The tissue-specific expression of Pb biosensors provides an excellent opportunity to explore the possible Pb-specific populations within living organisms. We believe that this integrated Pb biosensor system can be applied to the prevention of Pb poisoning and advanced research on Pb neurotoxicology.
2021-07-30 | Harnessing Peptides against lead pollution and poisoning: Achievements and prospects.
Among the broad applicability of peptides in numerous aspects of life and technologies, their interactions with lead (Pb), one of the most harmful substances to the environment and health, are constantly explored. So far, peptides were developed for environmental remediation of Pb-contaminations by various strategies such as hydrogelation and surface display. They were also designed for Pb detection and sensing by electrochemical and fluorescent methods and for modeling natural proteins that involve in mechanisms by which Pb is toxic. This review aims at summarizing selected examples of these applications, manifesting the enormous potential of peptides in the combat against Pb pollution. Nevertheless, the absence of new medicinal treatments against Pb poisoning that are based on peptides is noticeable. An overview of previous achievements utilizing Pb-peptide interactions towards various goals is presented and can be therefore leveraged to construct a useful toolbox for the design of smart peptides as next-generation therapeutics against Pb.
2019-11-04 | Therapeutic implications of how TNF links apolipoprotein E, phosphorylated tau, α-synuclein, amyloid-β and insulin resistance in neurodegenerative diseases.
While cytokines such as TNF have long been recognized as essential to normal cerebral physiology, the implications of their chronic excessive production within the brain are now also increasingly appreciated. Syndromes as diverse as malaria and lead poisoning, as well as non-infectious neurodegenerative diseases, illustrate this. These cytokines also orchestrate changes in tau, α-synuclein, amyloid-β levels and degree of insulin resistance in most neurodegenerative states. New data on the effects of salbutamol, an indirect anti-TNF agent, on α-synuclein and Parkinson's disease, APOE4 and tau add considerably to the rationale of the anti-TNF approach to understanding, and treating, these diseases. Therapeutic advances being tested, and arguably useful for a number of the neurodegenerative diseases, include a reduction of excess cerebral TNF, whether directly, with a specific anti-TNF biological agent such as etanercept via Batson's plexus, or indirectly via surgically implanting stem cells. Inhaled salbutamol also warrants investigating further across the neurodegenerative disease spectrum. It is now timely to integrate this range of new information across the neurodegenerative disease spectrum, rather than keep seeing it through the lens of individual disease states.
2016-05-24 | Lead Poisoning Disturbs Oligodendrocytes Differentiation Involved in Decreased Expression of NCX3 Inducing Intracellular Calcium Overload.
Lead (Pb) poisoning has always been a serious health concern, as it permanently damages the central nervous system. Chronic Pb accumulation in the human body disturbs oligodendrocytes (OLs) differentiation, resulting in dysmyelination, but the molecular mechanism remains unknown. In this study, Pb at 1 μM inhibits OLs precursor cells (OPCs) differentiation via decreasing the expression of Olig 2, CNPase proteins in vitro. Moreover, Pb treatment inhibits the sodium/calcium exchanger 3 (NCX3) mRNA expression, one of the major means of calcium (Ca(2+)) extrusion at the plasma membrane during OPCs differentiation. Also addition of KB-R7943, NCX3 inhibitor, to simulate Pb toxicity, resulted in decreased myelin basic protein (MBP) expression and cell branching. Ca(2+) response trace with Pb and KB-R7943 treatment did not drop down in the same recovery time as the control, which elevated intracellular Ca(2+) concentration reducing MBP expression. In contrast, over-expression of NCX3 in Pb exposed OPCs displayed significant increase MBP fluorescence signal in positive regions and CNPase expression, which recovered OPCs differentiation to counterbalance Pb toxicity. In conclusion, Pb exposure disturbs OLs differentiation via affecting the function of NCX3 by inducing intracellular calcium overload.
small molecules
2026-09-17 | Lead exposure decreases TPMT activity, highlighting the need for thiopurine dose adjustment in high-exposure individuals.
Thiopurine drugs are used for the treatment of a wide variety of diseases ranging from autoimmune diseases to various leukemia types. As efficacy of thiopurine drugs is significantly reduced by Thiopurine S-methyltransferase (TPMT)-mediated S-methylation, accurate assessment of individual TPMT-activity levels is crucial for optimizing thiopurine drug dosage regimens for each patient. Given its multifaceted regulation, identifying occupational exposures impacting TPMT enzymatic activity is crucial. The influence of lead(Pb2 +) on the enzymatic activity of TPMT was initially assessed in vitro, by spiking human blood having normal TPMT levels with increasing levels of Pb2+. The effect of occupational Pb2+-exposure on TPMT activity was further investigated by comparing blood TPMT activity levels of industrial workers prone to occupational Pb2+-exposure. Putative Pb2+-docking sites on TPMT enzyme were assessed through in silico analysis via MIB2 and CB-Dock2 servers. In vitro analysis indicated an inverse correlation between blood Pb2+-levels and TPMT-activity, which was further supported by in vivo analyses, providing evidence for Pb2+-mediated TPMT-inactivation. In silico Pb2+-docking analyses suggest two putative regions for Pb2+-mediated competitive TPMT-inhibition, four regions for direct/indirect inhibition, and four regions for allosteric inhibition. Further kinetic studies suggest that Pb2+ exerts its inhibitory effect through competition with SAM for the active site. The observed inverse correlation between blood Pb2+ and TPMT levels emphasizes the clinical importance of individualizing thiopurine drug dosage, especially for patients exposed to high levels of Pb2+. In vitro studies involving site-directed mutagenesis and analysis of patients with Pb2+-binding site mutations will validate the precise Pb2+-binding sites involved in TPMT-inhibition.
2026-09-08 | Therapeutics are needed to ameliorate neurobehavioral symptoms of developmental lead poisoning.
Developmental lead poisoning is a global problem and requires a global effort to remedy the environment and its effect on children. Until environmental lead is eliminated, therapeutics should be developed to alleviate symptoms of developmental lead poisoning. Memory and learning require adaptive oligodendrogenesis and neomyelination. Lead poisoning causes memory and learning deficits by targeting oligodendroglia lineage cells as well as other cells of the central nervous system. Though the etiologies of the various diseases and conditions that exhibit memory deficits being considered for treatment with pro-oligodendrogenesis therapeutics are different, the affected individuals share with those who have developmental lead intoxication the common symptoms of memory and cognitive deficits. Yet, unlike these maladies, there have not been any reports of studies exploring the use of pro-oligodendrogenesis drugs to ameliorate the memory/learning deficits in pediatric lead poisoning. The public health and science communities should recognize the consequence of developmental lead poisoning on society and deliver relief to the affected children with a low cost oral drug while maintaining the long term goal of ridding the planet of environmental lead contamination.
2026-09-04 | MORPHOLOGICAL CHARACTERISTICS OF REPARATIVE OSTEOGENESIS UNDER CONDITIONS OF CHRONIC LEAD INTOXICATION DURING PHARMACOLOGICAL CORRECTION IN AN EXPERIMENT
Aim — to assess the effect of combined metabolic correction (succinic acid, calcium citrate, vitamin D₃) on the morphological dynamics of reparative osteogenesis under ongoing lead intoxication. Materials and methods. Fifteen rats of experimental group II received water with lead acetate (50 mg/kg); after creation of a monocortical defect of the right femoral diaphysis (week 4, diameter 1.0 mm) the diet was supplemented with succinic acid (100 mg/kg), calcium citrate (200 mg/kg) and vitamin D₃ (500 IU/kg). Animals were withdrawn on days 7, 14, 21 and 28; sections were stained with haematoxylin–eosin and Masson trichrome (×100, ×400). Results. Under correction, repair proceeded more actively than in untreated animals: as early as day 7 angiogenesis and osteoblastic activity recovered, inflammatory infiltration and haemorrhages were absent, and cartilage fragments appeared. By days 14–21 a well-consolidated callus formed with compact, better-mineralised trabeculae and signs of woven-to-lamellar remodelling. By day 28 the callus consisted predominantly of mature lamellar bone with restored architecture, although isolated dystrophic osteocytes persisted. Conclusion. Combined metabolic correction substantially improves reparative osteogenesis under lead intoxication, bringing the morphological picture closer to physiological, yet not reaching the level of intact animals.
2026-09-04 | The Chemical Domino Effect: Lead Poisoning and the Collapse of Late Bronze Age Elites
Late Bronze Age collapse, Lead poisoning, Archaeometallurgy, Palace economies, Tin shortage
2026-09-03 | Ameliorative Role of fenugreek Oil Against Lead Acetate Trihydrate-Induced Hepatic, Renal and Testicular Injury in Wistar Albino Rats: Insights into Bcl-2 Expression and sodium/potassium balance.
Lead (Pb) is a prevalent environmental toxicant that induces multisystem toxicity, primarily through oxidative stress and apoptosis. Trigonella foenum-graecum L. (fenugreek) seed oil is enriched with bioactive phytoconstituents possessing potent antioxidant and anti-inflammatory properties. Therefore, this study was designed to investigate the protective effect of fenugreek oil against lead acetate trihydrate (PbAc)-induced hepatic, renal, and testicular histopathological damage in Wistar rats, with emphasis on the anti-apoptotic marker (Bcl-2). A total of 40 rats were randomly divided into four experimental groups (10 in each): a control group (CG), a Pb-intoxicated group (PbG) given 50 mg/kg of PbAc daily, a fenugreek oil-protected group (Pb + FOG) co-administered the same PbAc dose plus 250 mg/kg of fenugreek, and fenugreek oil-only group (FOG) receiving 250 mg/kg of fenugreek oil alone. All treatments were administered via oral gavage over a period of four weeks. Histopathological examination of the PbG revealed marked structural alterations in the hepatic tissue (necrosis, cytoplasmic vacuolation, and inflammatory cell infiltration), renal tissue (glomerular shrinkage and tubular degeneration), and testicular tissue (degeneration of the germinal epithelium and Leydig cells) compared to the CG. In contrast, co-administration of fenugreek seed oil in the Pb + FOG partially restored histological architecture of hepatic, renal and testicular tissues compared to the PbG. However, co-administration of fenugreek seed oil in the Pb + FOG significantly upregulated Bcl-2 mRNA expression compared to PbG (0.65 vs. 0.40; P < 0.01). Sequencing analysis of liver samples showed 97.81-100% nucleotide identity with the Bcl-2 mRNA reference sequence. Lead intoxication in the PbG significantly impaired serum biochemical parameters and elevated Na⁺, K⁺, and Pb levels compared to the CG and FOG. Conversely, co-administration of fenugreek seed oil in the Pb + FOG significantly reduced Pb concentration and restored Na⁺/K⁺ levels. In conclusion, concurrent administration of fenugreek seed oil may attenuate PbAc-induced hepatic, renal and testicular histopathological damage in rats. This protectivity effect was associated with the restoration of sodium/potassium balance, and upregulation of Bcl-2 expression. Nonetheless, further mechanistic studies, particularly addressing oxidative stress markers, are required.
oligonucleotides
2025-10-18 | Dual-Action Cellular Nanoparticles for Effective Lead (Pb2+) Detoxification.
Lead (Pb2+) exposure remains a persistent and serious public health concern due to its widespread presence and profound toxicity. Building on recent advances in toxin-neutralizing cell membrane-coated nanoparticles (CNPs) and the discovery of Pb2+-binding DNA aptamers, we develop dual-action neuron-mimetic CNPs for effective Pb2+ detoxification. In the formulation, the CNPs encapsulate aptamers within metal-organic framework (MOF) cores and coated with membranes derived from SH-SY5Y neuroblastoma cells, two functional components working together to neutralize Pb2+. The resulting constructs, termed Neuron-MOF/aptamer-NPs, exhibit strong Pb2+ binding capacity, excellent colloidal stability in physiological media, and resistance to DNA leakage. In vitro assays identify Neuron-MOF/aptamer-NPs as the most potent formulation, demonstrating dual-action neutralization against Pb2+-induced toxicity, oxidative stress, and lipid peroxidation in SH-SY5Y cells. In vivo, Neuron-MOF/aptamer-NP treatment significantly improves survival in a mouse model of lead poisoning and reduces hematologic, hepatic, and renal damage. Behavioral assessments further confirm the restoration of spatial memory and locomotor function. Neuron-MOF/aptamer-NPs exhibit no signs of acute toxicity in healthy mice. These findings establish Neuron-MOF/aptamer-NPs as a potent and biocompatible therapeutic platform for targeted lead detoxification with systemic and neuroprotective benefits.
2022-05-02 | Targeting CC chemokine ligand (CCL) 20 by miR-143-5p alleviate lead poisoning-induced renal fibrosis by regulating interstitial fibroblasts excessive proliferation and dysfunction.
Environmental lead contamination can cause chronic renal disease with a common clinical manifestation of renal fibrosis and constitutes a major global public health threat. Aberrant proliferation and extracellular matrix (ECM) accumulation in renal interstitial fibroblasts are key pathological causes of renal fibrosis. However, the mechanism underlying lead-induced kidney fibrosis remains unclear. The present study analyzed gene expression prolifes in lead acetate-treated primary mice renal interstitial fibroblasts and confirmed the aberrant expression of CC chemokine ligand (CCL) 20, one of the most obvious up-regulated genes. Analogously, lead acetate exposure dose-dependently increased CCL20 transcription, protein expression and release. Knockdown of CCL20 suppressed lead acetate-induced fibroblast proliferation, hydroxyproline contents, transforming growth factor-beta production and ECM-related protein (Collagen I and fibronectin) expression. Bioinformatics analysis predicted five top miRNAs targeting CCL20. Among them, miR-143-5p expression was dose-dependently decreased in lead acetate-treated fibroblasts. Mechanistically, miR-143-5p directly targeted CCL20. Elevation of miR-143-5p antagonized lead acetate-induced fibroblast proliferation, hydroxyproline and ECM-related protein expression, which were reversed by CCL20 overexpression. Additionally, CCL20 knockdown suppressed lead acetate-mediated Smad2/3 and AKT pathway activation. Notably, miR-143-5p overexpression attenuated the activation of the Smad2/3 and AKT pathway in lead acetate-exposed fibroblasts, which was counteracted by CCL20 elevation. miR-143-5p injection ameliorated renal fibrosis progression in mice in vivo. Thus, targeting CCL20 by miR-143-5p could alleviate renal fibrosis progression by regulating fibroblast proliferation and ECM deposition via the Smad2/3 and AKT signaling, providing a potential therapeutic target for environmental lead contamination-evoked fibrotic kidney disease.
2021-04-28 | Pb exposure triggers MAPK-dependent inflammation by activating oxidative stress and miRNA-155 expression in carp head kidney.
Lead (Pb) is a toxic heavy metal and an aquatic pollutant. Various amounts of heavy metals are released into the environment through industrial discharge, causing excessive contamination of aquatic ecosystems. The head kidney is a unique immune organ of the bony fish and plays an important role in the metabolism of heavy metals. Studies of toxic Pb exposure that have investigated the head kidney of carp are limited. This study was carried out to explore the potential immunotoxicity effects of Pb and the specific related mechanisms in the carp head kidney. Pb poisoning was shown to induce the production of reactive oxygen species (ROS) and increase the expression levels of phosphorylated proteins related to the MAPK pathway, including p38, extracellular signal-regulated protein kinase (ERK), and c-Jun N-terminal kinase (JNK). We also found that microRNA-155 played a key role in regulating the production of inflammatory factors TNF-α, IL-1β, and IL-6, and the pre-miRNA-155 inhibitor reversed the Pb-induced inflammation. In conclusion, these in vitro and in vivo findings suggest that oxidative stress and the MAPKs are involved in the Pb-induced inflammasome response, and the production of microRNA-155 aggravated the occurrence of inflammation in carp head kidney.
2019-03-18 | Chronic lead exposure decreases the expression of Huntingtin-associated protein 1 (HAP1) through Repressor element-1 silencing transcription (REST).
Chronic lead (Pb) exposure has been shown to reduce the expression of some synaptic proteins which are involved in vesicular trafficking and affect presynaptic neurotransmitter release. However, the precise mechanisms by Pb impairs neurotransmitter release are still not well defined. In the current study, we aimed to elucidate the changes of Huntingtin-associated protein 1 (HAP1) in Pb exposed rats and PC12 cells models and its molecular mechanism. Repressor element-1 silencing transcription (REST) modulates the expression of genes containing the repressor element 1 (RE-1) cis-regulatory DNA sequence. HAP1 promoter region contains a RE-1 binding motif. We also observed whether Pb exposure regulated the HAP1 transcription level through influencing the expression of REST. Mother rats were exposed to 0.5 and 2 g/L Pb acetate (PbAc) in drinking water from the first day of gestation until postnatal 21 days, then the offspring rats were continued to drink PbAc for 1 year, while the control groups received drinking water. PC12 cells were divided into 3 groups: 0 μM, 1 μM and 100 μM PbAc. The results revealed that Pb levels in blood and brain of Pb exposed groups were significantly higher than that of the control group. The ability of learning and memory in Pb exposed rats was decreased. Pb exposure reduced the expression of HAP1 and increased the REST expression. Silencing REST could reverse the decreasing of HAP1 in Pb exposed PC12 cells. Our findings raise a possibility that the decreasing of HAP1 expression by Pb exposure may affect neurotransmitter release and results in impairments in spatial learning and memory ability.
2018-12-28 | Lead exposure inhibits expression of SV2C through NRSF.
Lead (Pb) exposure has been shown to affect presynaptic neurotransmitter release in the animal and cell models. The mechanism by which Pb exposure impairs neurotransmitter release remains unknown. In this study, we aimed to investigate the effect of Pb exposure on synaptic vesicle protein 2C (SV2C) and its molecular mechanism. SV2C promoter region contains a neuron-restrictive silencer element (NRSE) binding motif. Neuron-restrictive silencer factor (NRSF) is a transcription repressor that regulates gene expression by binding to NRSE. We also observed whether Pb exposure regulates the transcriptional level of SV2C by influencing the expression of NRSF. Pregnant female rats were exposed to 0, 0.5 and 2.0 g/L lead acetate (PbAc) via drinking water from the first day of gestation until postnatal week 3. Neuro-2a (N2a) cells were divided into 3 groups: 0 μM (control group), 1 μM and 100 μM PbAc. Our data revealed that the ability of learning and memory in Pb-exposed rats were decreased, Pb exposure decreased SV2C expression and increased NRSF expression in the rat hippocampus and N2a cell. Silencing NRSF can reverse the down-regulation of Pb exposure on SV2C. These results indicate that Pb exposure can inhibit the transcription level of SV2C by up regulating the expression of NRSF. Decreased expression of SV2C can affect neurotransmitter release and synaptic transmission, which affect synaptic plasticity and then result in impairment of learning and memory.
cell therapies
2026-09-27 | Engineered Probiotics with Pb-Binding Enhanced Curli Nanofibers for Oral Lead Elimination.
Lead poisoning remains a persistent global health challenge. Current small-molecule chelation therapies for lead poisoning cause systemic side effects due to non-specific metal depletion. Here, we propose an "affinity-selectivity-safety" strategy using a living biointerface in which the probiotic is programmed to overexpress customized curli nanofibers. The high-affinity Pb-binding protein PbrR was anchored onto the cell surface of Escherichia coli Nissle 1917 (EcN) via fusion to the curli nanofiber subunit CsgA and presented within the extracellular self-assembled curli network. After induction, EcNC-P overexpresses the C-P fusion protein, which self-assembles into a dense and stable network of PbrR-functionalized curli nanofibers on the bacterial surface, without impairing bacterial viability, intestinal transit properties, or intrinsic probiotic functions. The engineered probiotics exhibited an exceptional Pb2+ binding capacity of up to 70 mg·g-1 biomass and preferential Pb selectivity over essential metals under competitive conditions. The curli-displayed PbrR provides an array of multidentate Pb2+-chelating sites, endowing the living material with an ultrahigh lead adsorption capacity. Orally ingested EcNC-P was completely excreted within 12 h, ensuring biosafety. In an acute oral Pb exposure mouse model, EcNC-P-based living materials achieved better efficacy than orally administered DTPA under the same dosing condition, reducing blood Pb levels by ∼30% and increasing fecal Pb excretion by ∼1.2-fold. Therapeutic supplementation of the probiotics promoted fecal lead excretion and markedly decreased tissue lead burdens and was associated with alleviated intestinal inflammation and altered gut microbiota composition. No systemic toxicity or adverse effects were observed with single high-dose use. This surface-anchored customized curli nanofiber probiotic integrates high-affinity lead chelation with the bioactivities of a living biointerface, offering a safe, oral, and programmable platform for the holistic management of lead poisoning.
2024-02-09 | Screening and Identification of Probiotic Lactobacilli from the Infant Gut Microbiota to Alleviate Lead Toxicity.
Lead (Pb2+) exposure cause a potential hazard to human health and the ecological environment; however, prevention and treatment of Pb2+ toxicity remain problems. The aim of this study is to isolate a novel probiotic lead (Pb2+)-resistant Lactobacillus strain from the infant gut microbiota and to determine whether they have the probiotic properties and investigate its preventive and therapeutic effects in the early-life Pb2+ exposure mouse model. In the present study, a total of 64 Pb2+-resistant colonies were isolated from the infant gut microbiota. Of these colonies, SYF-08, identified as Lacticaseibacillus casei, exhibited a Pb2+-binding capacity and Pb2+ tolerance. The in vivo study showed that SYF-08 treatment could effectively reduce Pb2+ levels in the blood, alleviate Pb2+ enrichment in bone and brain tissues, and recover the intestinal and brain damage in both dams and offspring. SYF-08 treatment also improved the antioxidant index in the liver and kidney tissues, while increasing the diversity of the intestinal microbiota of the offspring. The results of the in vitro and in vivo studies suggest that SYF-08, isolated from infant fecal samples, is a promising candidate probiotic against Pb2+ toxicity.
2023-02-06 | Lactobacillus fermentum HNU312 alleviated oxidative damage and behavioural abnormalities during brain development in early life induced by chronic lead exposure.
Lead exposure is a global public health safety issue that severely disrupts brain development and causes damage to the nervous system in early life. Probiotics and gut microbes have been highlighted for their critical roles in mitigating lead toxicity. However, the underlying mechanisms by which they work yet to be fully explored. Here, we designed a two-stage experiment using the probiotic Lactobacillus fermentum HNU312 (Lf312) to uncover how probiotics alleviate lead toxicity to the brain during early life. First, we explored the tolerance and adsorption of Lf312 to lead in vitro. Second, the adsorption capacity of the strain was determined and confirmed in vivo. The shotgun metagenome sequencing showed lead exposure-induced imbalance and dysfunction of the gut microbiome. In contrast, Lf312 intake significantly modulated the structure of the microbiome, increased the abundance of beneficial bacteria and short-chain fatty acids (SCFAs)-producing bacteria, and upregulated function-related metabolic pathways such as antioxidants. Notably, Lf312 enhanced the integrity of the blood-brain barrier by increasing the levels of SCFAs in the gut, alleviated inflammation in the brain, and ultimately improved anxiety-like and depression-like behaviours induced by lead exposure in mice. Subsequently, the effective mechanism was confirmed, highlighting that Lf312 worked through integrated strategies, including ionic adsorption and microbiota-gut-brain axis regulation. Collectively, this work elucidated the mechanism by which the gut microbiota mitigates the toxic effects of lead in the brain and provides preventive measures and intervention measures for brain damage due to mass lead poisoning in children.
2022-08-10 | Lactobacillus plantarum WSJ-06 alleviates neurobehavioral injury induced by lead in mice through the gut microbiota.
Chronic lead exposure can result in cognitive dysfunction and behavioral disorders. However, the current treatments for alleviating lead poisoning have many side effects. Previous studies have suggested that probiotics may have the potential to ameliorate neurotoxicity caused by lead exposure. This study determines the alleviating effects of Lactobacillus plantarum WSJ-06 on neurological disorders induced by chronic lead exposure from the perspective of the gut microbiota and serum metabolites. The results showed that treatment with Lactobacillus plantarum WSJ-06 alleviated memory dysfunction and reduced the levels of inflammatory cytokines in the serum and hippocampus induced by lead exposure. In addition, Lactobacillus plantarum WSJ-06 partially restored the lead-induced gut microbiota dysbiosis. It also increased the proportion of some beneficial metabolites in the serum, such as arachidonic acid, tryptophan hydroxylase, serotonin, vitamin B12, trehalose, and kynurenic acid, and decreased some metabolites in the serum, such as LPS 20:5 and L-kynurenine. A correlation analysis further indicated that lead-induced neurobehavioral disorders were related to intestinal microbiota (the [Eubacterium]_siraeum_group, Roseburia, Lactobacillus, etc) and serum metabolites (LPS 20:5, serotonin, vitamin B12, etc). In conclusion, Lactobacillus plantarum WSJ-06 alleviated neuroinflammation and memory impairment caused by lead exposure by modulating the gut microbiota and metabolites in the serum.
2019-10-29 | Bio‐Orthogonal Bacterial Reactor for Remission of Heavy Metal Poisoning and ROS Elimination
Multitudinous industrial products in daily life put human health at risk of heavy metal exposure, and natural bacteria have displayed superior performance in bioadsorption and biodegradation of heavy metal. In this study, a bacteria-based bioreactor is developed to precisely bioadsorb lead (Pb) ions, eliminate concomitant reactive oxygen species (ROS), and remit the injury of acute/chronic Pb poisoning. A nonpathogenic bacteria Escherichia coli MG1655 (Bac) is decorated with antioxidative cerium oxide nanoparticles (Ceria) on the surface through a bio-orthogonal reaction, and the complex bioreactor could spontaneously aggregate in organs with high concentration of Pb. Furthermore, the excess Pb is bioadsorbed by bacteria and the concomitant ROS is eliminated by Ceria nanoparticles. In vitro and in vivo studies demonstrate that this integral biotic/abiotic hybrid bioreactor successfully realizes detoxication of Pb and reparation of injury, also accompanied with inappreciable side effects.
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Drug Discovery Landscape
3 orphan drug designations for Lead poisoning, including 1 approved therapy.
3 orphan drug designations for Lead poisoning, including 1 approved therapy.
Drug | Therapy type | Orphan designation | Clinical trial status | Sponsor |
|---|---|---|---|---|
Erdosteine | small molecules | EMA | — | Rafifarm SRL |
ALPHA-1-ACID GLYCOPROTEIN | — | EMA | — | Bio Products Laboratory Limited |
Succimer [Chemet capsules] | small molecules | FDA | Approved | Bock Pharmacal Company |
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